Single-Nucleotide Polymorphisms in Human NPC1 Influence Filovirus Entry Into Cells.

Abstract	Niemann-Pick C1 (NPC1), a host receptor involved in the envelope glycoprotein (GP)-mediated entry of filoviruses into cells, is believed to be a major determinant of cell susceptibility to filovirus infection. It is known that proteolytically digested Ebola virus (EBOV) GP interacts with 2 protruding loops in domain C of NPC1. Using previously published structural data and the National Center for Biotechnology Information Single-Nucleotide Polymorphism (SNP) database, we identified 10 naturally occurring missense SNPs in human NPC1. To investigate whether these SNPs affect cell susceptibility to filovirus infection, we generated Vero E6 cell lines stably expressing NPC1 with SNP substitutions and compared their susceptibility to vesicular stomatitis virus pseudotyped with filovirus GPs and infectious EBOV. We found that some of the substitutions resulted in reduced susceptibility to filoviruses, as indicated by the lower titers and smaller plaque/focus sizes of the viruses. Our data suggest that human NPC1 SNPs may likely affect host susceptibility to filoviruses.
Authors	Tatsunari Kondoh, Michael Letko, Vincent J Munster, Rashid Manzoor, Junki Maruyama, Wakako Furuyama, Hiroko Miyamoto, Asako Shigeno, Daisuke Fujikura, Yoshihiro Takadate, Reiko Yoshida, Manabu Igarashi, Heinz Feldmann, Andrea Marzi, Ayato Takada
Journal	The Journal of infectious diseases (J Infect Dis) Vol. 218 Issue suppl_5 Pg. S397-S402 (11 22 2018) ISSN: 1537-6613 [Electronic] United States
PMID	30010949 (Publication Type: Journal Article, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
Chemical References	Carrier Proteins Intracellular Signaling Peptides and Proteins Membrane Glycoproteins NPC1 protein, human Niemann-Pick C1 Protein Receptors, Virus Viral Envelope Proteins
Topics	Animals Carrier Proteins (genetics) Cell Line Chlorocebus aethiops Ebolavirus (pathogenicity) HEK293 Cells Hemorrhagic Fever, Ebola (genetics, virology) Humans Intracellular Signaling Peptides and Proteins Membrane Glycoproteins (genetics) Niemann-Pick C1 Protein Polymorphism, Single Nucleotide (genetics) Receptors, Virus (metabolism) Vero Cells Viral Envelope Proteins (metabolism) Virus Internalization

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!